This newly initiated project has evolved from the young project on the Replication and Pathogenesis of Enveloped Viruses (ZO1 NS02791-01 LVMP). The main topic covered by this project focuses on the molecular virology of HIV, the AIDS virus, and on antiviral strategies designed to specifically interfere with the replication of HIV. It is our hope this interference with virus replication may cause a significant delay in the onset of AIDS or possibly prevent it. We are currently developing what we call pseudotypic defective interfering particles of HIV. The goal of this antiviral approach is to use these defective particles to target and specifically infect cells which are already infected by HIV. It is our anticipation that this cell-targeting will allow deliverance of genes and/or gene products specifically into HIV infected cells- The gene products are designed to interfere with the replication of HIV itself. In addition, we anticipate that these defective interfering HIV particles will not only down-regulate the number of HIV progeny but that they also will use HIV in an opportunistic way as their helper virus for their own assembly. This will permit repetition of this cycle in other HIV Infected cells We have succeeded by using our gene fusion method to construct the first prototype pseudotypic defective interfering HIV genome. The genome was assembled, cloned and sequenced and was found suitable for further evaluation as a targeted antiviral delivery system. We have also constructed two potential ribozymes which are designed to specifically cleave HIV genomic RNA, inactivate it and thereby increase the interfering potential of the defective virus. Functional tests are in progress.